Telocytes in human isolated atrial amyloidosis: ultrastructural remodelling.

The human heart can be frequently affected by an organ-limited amyloidosis called isolated atrial amyloidosis (IAA). IAA is a frequent histopathological finding in patients with long-standing atrial fibrillation (AF). The aim of this paper was to investigate the ultrastructure of cardiomyocytes and telocytes in patients with AF and IAA. Human atrial biopsies were obtained from 37 patients undergoing cardiac surgery, 23 having AF (62%). Small fragments were harvested from the left and right atrial appendages and from the atrial sleeves of pulmonary veins and processed for electron microscopy (EM). Additional fragments were paraffin embedded for Congo-red staining. The EM examination certified that 17 patients had IAA and 82% of them had AF. EM showed that amyloid deposits, composed of characteristic 10-nm-thick filaments were strictly extra-cellular. Although, under light microscope some amyloid deposits seemed to be located within the cardiomyocyte cytoplasm, EM showed that these deposits are actually located in interstitial recesses. Moreover, EM revealed that telopodes, the long and slender processes of telocytes, usually surround the amyloid deposits limiting their spreading into the interstitium. Our results come to endorse the presumptive association of AF and IAA, and show the exclusive, extracellular localization of amyloid fibrils. The particular connection of telopodes with amyloid deposits suggests their involvement in isolated atrial amyloidosis and AF pathogenesis.

Rare tumors of the heart--angiosarcoma, pericardial lipoma, leiomyosarcoma. Three case reports.

Primary tumors of the heart, pericardium and inferior vena cava are extremely rare. Three cases of surgically/biopsy proven angiosarcoma of the right atrium, pericardial lipoma and leiomyosarcoma of inferior vena cava--demonstrated by ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI)--are presented here.

Efficacy and tolerability of amlodipine/valsartan combination therapy in hypertensive patients not adequately controlled on amlodipine monotherapy.

UNLABELLED: ABSTRACT (ARB), in essential hypertensive patients not adequately controlled by amlodipine monotherapy. METHODS: This was a multi-centre, randomised, double-blind, active-controlled study in patients with essential hypertension. After a washout period followed by a single-blind amlodipine 10 mg run-in period, patients with mean sitting diastolic blood pressure (msDBP) > or =90 mmHg and <110 mmHg were randomised to receive amlodipine/valsartan (10/160 mg o.d.) or amlodipine (10 mg o.d.) for 8 weeks. TRIAL REGISTRATION NUMBER: NCT00171002. MAIN OUTCOME MEASURES: The primary efficacy variable was change from baseline in msDBP at study endpoint. Secondary efficacy variables were change from baseline in mean sitting systolic blood pressure (msSBP), responder rate (msDBP <90 mmHg or > or =10 mmHg reduction from baseline) and DBP control rate (msDBP <90 mmHg). RESULTS: Of the 1283 patients enrolled in single-blind period, 944 were randomised to receive amlodipine/valsartan 10/160 mg (n = 473) and amlodipine 10 mg (n = 471). Statistically significant greater reductions (p < 0.0001) from baseline in msSBP/msDBP were observed with combination therapy (12.9/11.4 mmHg) compared to monotherapy (10.0/9.3 mmHg). Responder rate was significantly greater (p = 0.0011) with combination therapy (79.0%) compared to monotherapy (70.1%). The percentage of patients with controlled DBP was also significantly (p < 0.0001) higher with combination therapy (77.8%) compared to monotherapy (66.5%). Incidence of peripheral oedema was slightly higher with amlodipine monotherapy (9.4%) compared to combination therapy (7.6%). CONCLUSION: The combination of amlodipine/valsartan in this 8-week double-blind study provided additional BP control and was well tolerated in patients inadequately controlled with amlodipine monotherapy. Results should be interpreted with the knowledge that study entry criteria may limit application to a wider population.

The electrocardiographic abnormalities in highly trained athletes compared to the genetic study related to causes of unexpected sudden cardiac death.

BACKGROUND: Electrocardiograms in elite endurance athletes sometimes show bizarre patterns suggestive of inherited channelopathies (Brugada syndrome, long QTc, catecholaminergic polymorphic ventricular tachycardia) and cardiomyopathies (arrhythmogenic right ventricular cardiomyopathy, hypertrophic cardiomyopathy) responsible for unexpected sudden cardiac death. Among other methods, genetic analyses are required for correct diagnosis. OBJECTIVE: To correlate 12-lead electrocardiographic patterns suggestive of inherited channelopathies and cardiomyopathies to specific genetic analyses. DESIGN: Prospective study (2004-2007) of screening 12-lead ECG tracings in standard position and higher intercostal spaces V1 to V3 precordial leads, performed in athletes and normal sedentary subjects aged match. Genetic analyses of subjects with ECG abnormalities suggested inherited channelopathies and cardiomyopathies. SETTING: All cardiologic exams and electrocardiograms were performed at "Prof. Dr. C.C. Iliescu" National Institute of Cardiovascular Diseases (Bucharest, Romania). The genetic studies were done at "Mina Minovici" National Institute of Forensic Medicine (Bucharest, Romania). PARTICIPANTS: 347 elite endurance athletes (seniors--190, juniors--157), mean age of 20; 200 subjects mean age of 21, belonging to the control group of 505 normal sedentary population. RESULTS: Seniors. RSR' (V1 to V3) pattern, in 45 cases (23.68%), 5 of them with questionable Brugada sign (elevated J wave and "coved" ST segment, < 2 mm in one lead, V1. Typically, Brugada 1 sign was found in one case (0.52%) with no SCN5A abnormalities. One athlete (0.52%) had normal ECG and exon1 SCN5A duplication. MRI confirmed three arrhythmic right ventricular cardiomypathy epsilon waves (1.57%), in one case. ST-segment elevation myocardial injury like in V1-V3 precordial leads in 34 athletes (17.89%). Genetic analyses-no gene mutations. Juniors. Upright J wave was found in 43 cases (27.38%). Convex ST segment elevation in V1-V3/V4, in 39 cases (24.84%). Bifid T wave with two distinct peaks was found in 39 cases (24.84%), 5 of them with mild prolonged QTc (0.48"-0.56") and KCN genes mutations. Nine (5.73%) of the elevated ST segment juniors had questionable Brugada sign, two of which with KCN (n=1) and SCN5A (n=1) gene mutations. Ajmaline provocative test was negative in 4 and was refused by 5 subjects. CONCLUSION: Bizarre QRS, ST-T patterns suggestive of abnormal impulse conduction in the right ventricle, including the right outflow tract, associated with prolonged QTc interval in some cases were observed in highly trained endurance athletes. The genetic analyses, negative in most athletes, identified surprising mutations in SCN5A and KCN genes in some cases.

Interstitial Cajal-like cells (ICLC) in myocardial sleeves of human pulmonary veins.

We present here evidence for the existence of a new type of interstitial cell in human myocardial sleeves of pulmonary veins: interstitial Cajal-like cell (ICLC). This cell fulfils the criteria for positive diagnosis of ICLC, including CD 117/c-kit positivity. Transmission electron microscopy revealed typical ICLC with 2 or 3 very long processes (several tens of mm) suddenly emerging from the cellular body. Also, these processes appear moniliform but extremely thin (0.1-0.4 mm) under the resolving power of the usual microscopy. Cell processes establish close spatial relationships between each other, as well as with capillaries and nerve endings. ICLC appear located among the myocardial cells and particularly at the border between the myocardial sleeve and pulmonary vein wall.

Recurrent atrial myxoma.

We have chosen this case of sporadic atrial myxoma for our presentation because it had a particular evolution, with recurrence at 8 years after surgical excision (echocardiography was performed every year) and a particular diagnostic means - at echocardiographic follow-up, the patient being asymptomatic. This presentation, together with a review of literature included in the article, emphasizes the importance of a careful postoperative follow-up of the patients and the existence of some particular aspects of the evolution and symptomatology of recurrent atrial myxoma.

Clinical results of the Pop De Popa xenobioprosthesis in patients with advanced heart failure: long-term follow-up of 562 patients.

From January of 1984 through December of 1990, we implanted 739 Pop De Popa wild boar aortic valves in 626 patients, in all cardiac valvular positions. Of these patients, 562 received only the Pop De Popa xenobioprostheses, which numbered 620 valves. Only patients with contraindications for bioprosthetic valves (such as children under the age of 15) were excluded. At surgery, the 562 patients ranged in age from 17 to 66 years (mean, 41.7 yrs). Five hundred thirty-one (94.48%) were in NYHA functional class III or IV before valve replacement. Of the 620 valves implanted, 20 were replacements for Pop de Popa prostheses and the other 600 were replacements for native valves. Survivors were followed-up for a mean period of 31.6(+/-22) months (range, 3 months to 7 years), and for a cumulative period of 2,432 patient-years. Over the 7-year period of study, there were 78 late deaths, and 32 other patients were lost to follow-up. The analysis demonstrated good cardiac and general improvement. At the conclusion of the 7-year study, 94.83% of the survivors subject to follow-up were in NYHA functional class I or II. The early mortality rate was 12% (68 patients), and the following incidence of early valve-related complications was noted: thromboembolism, 3% to 4%; endocarditis, 1% to 2%; paravalvular leak, 1% to 2%; primary tissue failure, 1%; and anticoagulant-related hemorrhaging, 1%. At 7 years, 90% of survivors subject to follow-up were still free of valve failure. The probability of complications was as follows: thromboembolism, 16.1%; endocarditis, 8.8%; paravalvular leak, 4.4%; anticoagulant-related hemorrhaging, 1.2%; and valvular degeneration and reoperation, 12.5%. The probability of survival at 7 years was 86.12%. While this study does not yet demonstrate the superiority of the wild boar valve over other bioprosthetic valves, it does reaffirm the worth of implanting biologic valves in adult patients when not contraindicated. Perhaps as we continue follow-up beyond 7 years, the apparent durability of the wild boar cusps will manifest itself in a statistically significant manner.